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Background Women with endometrial cancer (EC) have favorable prognoses, leaving them vulnerable to the development of second primary cancers (SPCs). We investigated the SPC risk and survival outcomes among EC patients treated with surgery alone in order to exclude the impact of adjuvant treatment on the results. Methods Data from the Taiwan Cancer Registry from 1995 to 2013 were analyzed. Standardized incidence ratios (SIRs) of SPCs among EC survivors were calculated. Results Among 7725 women enrolled, 478 developed an SPC. The overall SIR for SPCs in EC survivors was 2.84 (95% confidence interval [CI] 2.59–3.10) compared with the general female population. Women diagnosed with EC at age

Objective To report two cases of for primary peritoneal serous carcinoma (PPSC) to present with gastrointestinal manifestations that mimic colorectal cancer. Case report There were two patients with initial presentations of fatigue with iron deficiency anemia, and tenesmus with bloody stool. Tumors of the ascending colon and rectum were detected by colonofiberoscope, and pathologic reports of tumor biopsies revealed adenocarcinoma of suspected gynecologic origin. Both patients underwent optimal debulking surgery without macroscopic residual tumor, and then received adjuvant carboplatin and paclitaxel chemotherapy with bevacizumab. Conclusions PPSC can clinically present like primary colorectal carcinoma. The differential diagnosis requires special staining of several markers for tumor tissues.

Low-grade ovarian serous carcinoma (LGSOC) has clinical features different from high-grade serous ovarian carcinoma (HGSOC) accounting for the majority of epithelial ovarian cancer. Because of its rarity, previous studies have only focused on the high-grade disease without considering the differences between the two subtypes. This study aimed to evaluate the effect of the clinical prognostic factors known for HGSOC on survival in patients with LGSOC. Based on the Federation of Gynecology and Obstetrics (FIGO) stage, progression-free survival (PFS) was markedly decreased in advanced disease compared with early disease. For stage I, patients with stage IC had poorer survival than those with stage IA and IB regardless of the number of cycles of adjuvant chemotherapy. For advanced disease, no gross residual disease after primary cytoreductive surgery was significantly associated with longer PFS when compared with gross residual disease. In multivariate analysis for PFS and overall survival (OS), age, preoperative CA-125, time interval from surgery to chemotherapy, and the number of cycles of adjuvant chemotherapy were not associated with prognosis. Complete cytoreduction was the only independent prognostic factor for PFS (HR 2.45, p = 0.045). Our study revealed that the known prognostic factors in HGSOC did not show any effect on the survival in LGSOC except for FIGO stage and complete cytoreduction.

BACKGROUND: Positron emission tomography (PET)/MRI biomarkers have been shown to have prognostic significance in patients with cervical cancer. Their associations with progression-free survival (PFS) and overall survival (OS) merit further investigation. PURPOSE: To evaluate the association between PET/MRI biomarkers and tumor stage, PFS, and OS in patients with cervical cancer. STUDY TYPE: Prospective cohort study. POPULATION: In all, 54 patients with newly diagnosed cervical cancer and measurable tumors (>1 cm) were included in the image analysis. FIELD STRENGTH/SEQUENCE: 3.0T integrated PET/MRI including diffusion-weighted echo-planar imaging (b = 50 and 1000 s/mm2 ) and [18F]fluorodeoxyglucose PET. ASSESSMENT: Two radiologists measured the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean ), maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. STATISTICAL TESTS: A Mann-Whitney U-test was used to evaluate the association between the imaging biomarkers and tumor stage. A Cox proportional hazards model was used to assess the relationships between the imaging biomarkers and survival. RESULTS: In advanced tumors (T ≥ 1b2, M1, stage ≥ IB3), ADCmin was significantly lower and MTV, TLG, MTV/ADCmin , and TLG/ADCmin were significantly higher (P values between

Peritoneal tuberculosis (PTB) is an uncommon extrapulmonary infection mimickng primary peritoneal cancer (PPC). We retrospectively included 23 women with PTB and 47 women with PPC treated in a medical center to study the clinical and radiological features that differentiate PTB from PPC. Body temperature above 38 °C was a unique feature of PTB (34.7% versus 0%, p &lt, 0.001). Body Mass Index (BMI) was lower (21.9 ± 3.7 versus 25.2 ± 4.1, p = 0.003), white blood cell (WBC) count was lower (5179.6 ± 1502.2 versus 7716.2 ± 2741.8, p &lt, 0.001), and CA-125 level was lower (508.0 ± 266.1 versus 2130.1 ± 2367.2 U/mL, p &lt, 0.001) in PTB compared with PPC. Imaging detected more pulmonary infiltration and consolidation (52.2% versus 6.4%, p &lt, 0.001), and less omental/mesentery changes (52% versus 83%, p &lt, 0.001) in PTB compared with PPC. The operated patients received earlier treatment compared to patients without operation (7.9 ± 5.3 days versus 17.2 ± 11.0 days, p = 0.010). In conclusion, fever above 38 °C, lower BMI, lower WBC count, less elevated CA-125 level, and imaging of less omental involvement were features of PTB differentiated from PPC.

Epithelial ovarian cancer (EOC) patients are generally diagnosed at an advanced stage, usually relapse after initial treatments, which include debulking surgery and adjuvant platinum-based chemotherapy, and eventually have poor 5-year survival of less than 50%. In recent years, promising survival benefits from maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) has changed the management of EOC in newly diagnosed and recurrent disease. Identification of BRCA mutations and/or homologous recombination deficiency (HRD) is critical for selecting patients for PARPi treatment. However, the currently available HRD assays are not perfect predictors of the clinical response to PARPis in EOC patients. In this review, we introduce the concept of synthetic lethality, the rationale of using PARPi when HRD is present in tumor cells, the clinical trials of PARPi incorporating the HRD assays for EOC, the current HRD assays, and other HRD assays in development.

Central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) are rare. We investigated the clinico-pathological prognostic factors of patients with CNS metastases from EOC and compared the outcomes of various treatment modalities. We retrospectively reviewed the records of patients with CNS metastases from EOC between 2000 and 2020. Information on the clinical and pathological characteristics, treatment, and outcomes of these patients was retrieved from Samsung Medical Center and National Taiwan University Hospital. A total of 94 patients with CNS metastases were identified among 6,300 cases of EOC, resulting in an incidence of 1.49%. Serous histological type [hazard ratio (HR): 0.49 (95% confidence interval [CI] 0.25-0.95), p=0.03], progressive disease [HR: 2.29 (95% CI 1.16-4.54), p=0.01], CNS involvement in first disease relapse [HR: 0.36 (95% CI 0.18-0.70), p=0.002], and gamma knife radiosurgery (GKS)-based combination treatment for EOC patients with CNS lesions [HR: 0.59 (95% CI 0.44-0.79), p

Ewing sarcoma and peripheral primitive neuroectodermal tumor constitute the Ewing family of tumors (EFT). EFTs primarily arising in the ovary are extremely rare. We report the case of a 22-yr-old nulliparous woman with a primary EFT in the ovary that initially presented as a 3-cm teratoma-like ovarian tumor, with rapid progression to a 15-cm-sized tumor with liver metastasis in 3 mo. The patient underwent suboptimal debulking surgery and salvage chemotherapy with vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide. In conclusion, primary EFT in the ovary is extremely rare with highly aggressive behavior and poor outcome for metastatic disease. Demonstration of EWSR1 rearrangement, observed in a variety of soft tissue tumors, is very helpful in the diagnosis of EFT when interpreted on the basis morphology and immunohistochemistry.

AimTo retrospectively investigate the pre-operative clinical factors and ultrasonographic features that influence the accuracy of the intraoperative frozen section (IFS) of ovarian tumors.Patients and methodsWomen with ovarian tumors that underwent IFS in one tertiary medical center were recruited from January 2010 to December 2018. Demographic and clinical data of these women were retrieved from medical records in the hospital’s centralized database.ResultsA total of 903 ovarian tumors were enrolled, including 237 (26.2%) benign, 150 (16.6%) borderline tumor, and 516 (57.2%) malignant. The overall accuracy of IFS among all specimens was 89.9%. The sensitivities of IFS in diagnosing borderline tumors (82.0%) and malignant tumors (88.2%) were lower than in diagnosing benign tumors (98.7%, p vs. 51.5 ± 11.8 years, p = 0.013, Mann–Whitney U test), and higher percentage of early-stage disease (85.2% vs. 65.1%, p = 0.001, chi-square test) and mucinous (39.3% vs. 3.3%) and endometrioid histologic types (34.4% vs. 20.2%) than the concordant group (all by chi-square test). Menopause (OR 0.34, 95% CI 0.15–0.76, p = 0.009), multicystic tumor in ultrasound (OR 2.14, 95% CI 1.14–4.01, p = 0.018), and ascites existence (OR 0.33, 95% CI 0.14–0.82, p = 0.016) were factors related to the discordant IFS by multivariate analysis.ConclusionsIFS has good accuracy in the diagnosis of ovarian tumors. We recommend more frozen tissue sampling for sonographic multicystic tumors in premenopausal women to improve the accuracy of IFS.

We aimed to evaluate factors influencing the outcomes of patients with platinum-sensitive recurrent epithelial ovarian carcinoma (EOC). Patients with advanced-stage EOC, who received debulking surgery and adjuvant chemotherapy for recurrence, were obtained from the National Health Insurance Research database of Taiwan between 2000 and 2013. A total of 1038 patients with recurrent advanced-stage EOC were recruited. The platinum + paclitaxel (PT) group had the best five-year overall survival (OS) compared with the other three groups (p &lt, 0.001). The hazard ratios (HRs) of five-year OS for the platinum + liposomal doxorubicin (PD), topotecan (TOP), and pegylated liposomal doxorubicin (PLD) groups were 1.21 (p = 0.07), 1.35 (p = 0.016), and 1.80 (p &lt, 0.001), respectively, compared with the PT group. The PT group also had lower hazard ratios of five-year OS for patients with platinum therapy-free interval (TFIp) between 6 and 12 months compared with the other three groups (p &lt, 0.0001). However, the HRs of five-year OS did not differ between the PT and PD groups in patients with TFIp &gt, 12 months. Patients with TFIp &gt, 12 months had lower HRs of five-year OS compared with those with TFIp of 6–12 months, regardless of whether they were treated with platinum-based (p = 0.001) or non-platinum-based (p = 0.003) regimens. Chemotherapeutic regimens and TFIp influenced the outcomes of patients with recurrent EOC. For patients with TFIp of 6–12 months, the PT regimen is the first choice based on their best overall survival result. For patients with TFIp &gt, 12 months, either platinum-based or non-platinum regimens could be used because of their similar excellent overall survival.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI), low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS), patients with age &gt, 60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.

Objective Cytoreductive surgery followed by adjuvant chemotherapy is a standard frontline treatment for epithelial ovarian cancer (EOC). We aimed to develop an ovarian cancer risk score (OVRS) based on the expression of 10 ovarian-cancer-related genes to predict the chemoresistance, and outcomes of EOC patients. Methods We designed a case-control study with total 149 EOC women including 75 chemosensitives and 74 chemoresistants. Gene expression was measured using the quantitative real-time polymerase chain reaction. We tested for correlation between the OVRS and chemosensitivity or chemoresistance, disease-free survival (DFS), and overall survival (OS), and validated the OVRS by analyzing patients from the TCGA database. Results The chemosensitive group had lower OVRS than the chemoresistant group (5 vs. 15, p≤0.001, Mann-Whitney U test). Patients with disease relapse (13 vs. 5, p60 months) of patients with OVRS ≥10 were significantly shorter than those of patients with OVRS

Background The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. Methods We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. Results One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. Conclusions Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. Trial registration ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.

Objective: To evaluate the clinical presentations, diagnosis, management, and outcomes of torsion of the pedunculated subserous uterine leiomyoma. Materials and methods: We retrospectively reviewed medical records of patients with subserous uterine leiomyomas undergoing surgeries at National Taiwan University Hospital from January 2001 to December 2015. Results: Five cases of torsion of pedunculated subserous uterine leiomyoma were identified. All presented with sudden onset abdominal pain. Two patients received emergent surgeries, the other three cases received scheduled surgeries. The postoperative courses of these five women were uneventful without sequelae. Conclusions: Torsion of pedunculated subserous uterine leiomyoma is rare. Accurately diagnosing it prior to surgery is a major challenge. It should be one of the differential diagnosis in patients with uterine leiomyoma presenting with acute abdomen. Keywords: Abdominal pain, Emergency, Myomectomy, Subserous leiomyoma, Torsion

Objective To report a case and review published cases of large cell neuroendocrine carcinoma (LCNEC) of the endometrium. Case report A 51-year-old female presented with postmenopausal bleeding and a palpable pelvic mass. An endometrial biopsy showed a malignant mixed Mullerian tumor (MMMT). Suboptimal debulking surgery was performed. The final pathology revealed stage IVB endometrial LCNEC. Post-operative adjuvant chemotherapy with cisplatin and etoposide was administered. Two months after discontinuing adjuvant chemotherapy, salvage chemotherapy with cisplatin and ifosfamide was administered due to tumor progression; however, obstructive ileus was noted 2 months later. A segmental small bowel resection and palliative colostomy were performed. She died secondary to a post-operative infection 8 days after the operation. Conclusion Endometrial LCNEC is a rare but aggressive disease. If diagnosed, combined therapies, including staging surgery, following by adjuvant radiotherapy and chemotherapy, should be performed.

Objective: To evaluate the influence of age, screening interval, and histologic type on the effect of Pap smears in cervical cancer screening. Materials and methods: Data were retrieved from the Taiwan National Cancer Registry and Cervical Cancer Screening Registration System for the period from 2002 to 2010. Age, Pap smear interval, FIGO stage, and histology were further analyzed. Results: A total of 12,294 women with cervical cancer were enrolled, including 10,040 with squamous cell carcinoma (SCC), 1720 with adenocarcinoma (ADC), 401 with adenosquamous carcinoma (ASC), and 133 with small cell neuroendocrine carcinoma (SMC). Women who had a Pap smear at an interval of

Adjuvant treatment in advanced-stage (stages III /IV) endometrial carcinomas in terms of tumor grades has not yet been explored. We retrospectively analyzed 194 patients with advanced-stage endometrioid endometrial carcinoma who received surgery, followed by adjuvant therapy, at National Taiwan University Hospital between January 1, 2000 and August 31, 2017. Adjuvant therapies included radiation (RT), chemotherapy alone (CT), and combined modality treatment (CMT: radiation and chemotherapy). The prognostic factors were determined from multivariate survival analyses using Cox regression models. Progression-free survival (PFS) and overall survival (OS) times were estimated with the Kaplan&ndash, Meier method. The median follow-up was 45.5 months (range: 6.2&ndash, 207.9). In grade 1/2 endometrioid carcinoma, neither adjuvant CT nor CMT could prolong PFS significantly compared to RT (CT: HR 1.59, 95% CI 0.64&ndash, 3.97, CMT: HR 2.03, 95% CI 0.72&ndash, 5.74). Notably, maximal cytoreduction independently improved PFS (HR 0.31, 95% CI 0.10&ndash, 0.90). No particular adjuvant treatment provided an OS advantage over the others for grade 1/2 endometrioid carcinomas. However, for grade 3 endometrioid carcinoma, CMT showed OS benefits (HR 0.15, 95% CI 0.03&ndash, 0.89) compared to RT and CT. In conclusion, maximal cytoreduction should be the goal in patients with grade 1/2 advanced-stage endometrioid carcinomas. Based on our results, patients with grade 3 endometrioid carcinomas might benefit from adjuvant CMT.

In this retrospective study, we investigated adverse events and outcomes in patients treated with bevacizumab for ovarian, fallopian tube, or primary peritoneal cancers at a single hospital. We determined the cumulative incidences of various bevacizumab-related adverse events and the correlation between dose and adverse event incidences. We analyzed data from 154 patients that received 251 rounds of bevacizumab as first-line, first salvage, >2 salvage treatments. Adverse events of any grade were observed in 121 (78.6%) patients; at least one grade 3 or 4 adverse event occurred in 32 (20.8%) patients. The two most common events were proteinuria (38.3%) and hypertension (33.8%). The first-line treatment group displayed significantly higher frequencies of hypertension (52.7% vs. 18.9% vs. 15.5%, p < 0.001), wound complications (9.1% vs. 0% vs. 1.2%, p = 0.010), arthralgia (29.1% vs. 11.3% vs. 8.3%, p = 0.003), and reduced range of joint motion (14.5% vs. 5.7% vs. 3.6%, p = 0.046), compared to those in the first and >2 lines salvage groups, respectively (Kruskal–Wallis test). The cumulative incidences of all grades and grades 3/4 of hypertension cumulative incidence plateaued at around 30% for all grades and 10% for grades 3 and 4, at bevacizumab doses above 8080 and 3510 mg, respectively. The proteinuria cumulative incidence plateaued at around 35% for all grades and 3% for grades 3 and 4, at bevacizumab doses above 11,190 and 4530 mg, respectively. We concluded that, in this realistic clinical population, different kinds and higher cumulative incidences of adverse events were observed compared to those reported in previous clinical trials. Moreover, bevacizumab doses showed cumulative toxicity and plateau effects on hypertension and proteinuria.

Epithelial ovarian cancer patients usually relapse after primary management. We utilized the support vector machine algorithm to develop a model for the chemo-response using the Cancer Cell Line Encyclopedia (CCLE) and validated the model in The Cancer Genome Atlas (TCGA) and the GSE9891 dataset. Finally, we evaluated the feasibility of the model using ovarian cancer patients from our institute. The 10-gene predictive model demonstrated that the high response group had a longer recurrence-free survival (RFS) (log-rank test, p = 0.015 for TCGA, p = 0.013 for GSE9891 and p = 0.039 for NTUH) and overall survival (OS) (log-rank test, p = 0.002 for TCGA and p = 0.016 for NTUH). In a multivariate Cox hazard regression model, the predictive model (HR: 0.644, 95% CI: 0.436&ndash, 0.952, p = 0.027) and residual tumor size &lt, 1 cm (HR: 0.312, 95% CI: 0.170&ndash, 0.573, p &lt, 0.001) were significant factors for recurrence. The predictive model (HR: 0.511, 95% CI: 0.334&ndash, 0.783, p = 0.002) and residual tumor size &lt, 1 cm (HR: 0.252, 95% CI: 0.128&ndash, 0.496, p &lt, 0.001) were still significant factors for death. In conclusion, the patients of high response group stratified by the model had good response and favourable prognosis, whereas for the patients of medium to low response groups, introduction of other drugs or clinical trials might be beneficial.

The objective of this article was to report the clinicopathological characteristics, treatment modalities, and outcomes of patients with clear cell carcinoma (CCC) of the abdominal wall. Medical records of six patients diagnosed with CCC of the abdominal wall between May 2003 and May 2018 at the National Taiwan University Hospital were reviewed. All patients had prior obstetric or gynecologic surgeries. The primary clinical presentation was enlarging abdominal masses at previous surgical scars. Four patients underwent initial/primary surgeries with/without adjuvant chemotherapy. One patient received neoadjuvant chemotherapy followed by surgical intervention and adjuvant chemotherapy, the other received chemotherapy and sequential radiotherapy without any surgical intervention. Two of four patients undergoing initial/primary surgeries had disease recurrence and the remaining two cases without initial surgery experienced disease progression during primary treatment. Inguinal lymph nodes were the most frequent sites of recurrence. In conclusion, previous obstetric or gynecologic surgery can be a risk factor for CCC of the abdominal wall. Complete resection of abdominal wall tumor and suspected intra-abdominal lesions with hysterectomy and bilateral inguinal lymph nodes dissection may be the primary treatment. Adjuvant chemotherapy would be considered for potential benefits. For patients without bilateral inguinal lymph nodes dissection, careful inguinal lymph node palpation during postoperative surveillance is necessary. More cases are still needed to elucidate the clinical management of this disease.

We aimed to investigate the outcomes and subsequent pregnancies of early-stage cervical cancer patients who received conservative fertility-sparing surgery. Women with early-stage cervical cancer who underwent conservative or fertility-sparing surgery in a tertiary medical center were reviewed from 2004 to 2017. Each patient&rsquo, s clinicopathologic characteristics, adjuvant therapy, subsequent pregnancy, and outcome were recorded. There were 32 women recruited, including 12 stage IA1 patients and 20 stage IB1 patients. Twenty-two patients received conization/LEEP and the other 10 patients received radical trachelectomy. Two patients did not complete the definite treatment after fertility-sparing surgery. There were 11 women who had subsequent pregnancies and nine had at least one live birth. The live birth rate was 73.3% (11/15). We conclude that patients with early-stage cervical cancer who undergo fertility-sparing surgery can have a successful pregnancy and delivery. However, patients must receive a detailed consultation before surgery and undergo definitive treatment, if indicated, and regular postoperative surveillance.

Aim: To investigate the CDH1, DLEC1 and SFRP5 gene methylation panel for advanced epithelial ovarian carcinoma (EOC). Materials & methods: One hundred and seventy-seven advanced EOC specimens were evaluated by methylation-specific PCR. We also used The Cancer Genome Atlas dataset to evaluate the panel. Results: The presence of two or more methylated genes was significant in recurrence (hazard ratio [HR]: 1.91 [1.33–2.76]; p = 0.002) and death (HR: 1.96 [1.26–3.06]; p = 0.006) in our cohort. In The Cancer Genome Atlas dataset, the presence of two or three methylated genes was significant in death (HR: 1.59 [1.15–2.18]; p = 0.0047) and close to the significance level in recurrence (HR: 1.37 [0.99–1.88]; p = 0.058). Conclusion: The CDH1, DLEC1 and SFRP5 methylation panel is a potential prognostic biomarker for advanced EOC.

We aimed to identify factors predicting parametrial invasion in early-stage cervical cancer patients undergoing radical hysterectomy. We recruited women with invasive cervical cancer who underwent radical hysterectomy at a single medical institute from 2000-2011. The clinical and pathological characteristics and outcomes were retrospectively recorded, and the risk factors for parametrial invasion were analyzed. We enrolled 339 patients, including 7 with stage IA1 carcinomas, 10 with stage IA2, 266 with stage IB1, 39 with stage IB2, 14 with stage IIA1, and 3 with stage IIA2. The majority (237/339, 69.9%) had squamous cell carcinoma, while 32 (12.4%) had parametrial invasion. The 16 patients with stage IB1 tumors and parametrial invasion were older (55.9±9.5vs. 49.0±9.9 years, p = 0.005, Mann-Whitney U test), and had deeper cervical stromal invasion (9.59±4.87 vs. 7.47±5.48 mm, p = 0.048, Mann-Whitney U test), larger tumor size (2.32±1.15 vs. 1.74±1.14cm, p = 0.043, Mann-Whitney U test), higher incidences of lymphovascular space invasion (87.5% vs. 28.8%, p2 cm,10% had parametrial invasion and 24.2% had lymph node metastasis compared with only 4% and 9.4% of stage IB1 patients with a tumor size

Heme oxygenase (HO)-1 is upregulated by many stressful stimuli, including arsenic. A GT-repeat ((GT)n) polymorphism in the HO-1 gene promoter inversely modulates the levels of HO-1 induction. Previous HO-1 (GT)n polymorphism studies in relation to cancer risk have shown disparate results. We prospectively investigated the associations between HO-1 (GT)n polymorphism and cancer risk related to arsenic from drinking water. Totally, 1,013 participants from community-based cohorts of arseniasis-endemic areas in Taiwan were followed for 13 years. Allelic polymorphisms were classified into long (L, ≥ 27 (GT)n) and short (S, 300 μg/L) had a greater risk of skin cancer compared to the genotype alone. Consistent with previous findings, participants with the S-allele had a reduced risk of lung adenocarcinoma (HR = 0.21; 95% CI: 0.03-0.68) versus those with L/L genotype. There were no significant differences in risk of urothelial carcinoma among the three genotypes. Associations of HO-1 (GT)n polymorphism with cancer risk differs by histological subtype and the polymorphism should be considered a modifier in the risk assessment of arsenic exposure.

We propose CHI3L1 as a prognostic biomarker for patients with epithelial ovarian carcinoma (EOC) and also suggest possible biological functions of CHI3L1. We measured CHI3L1 expression with quantitative real time-polymerase chain reaction (qRT-PCR) in 180 women with EOC and evaluated correlations between CHI3L1 expression, clinicopathological characteristics, and the outcomes of the patients. The expression of CHI3L1 was higher in cancerous tissues than in normal tissues. The expression of CHI3L1 was also higher in patients with a serous histological type, advanced stage, and chemoresistance. Patients with high CHI3L1 expression had a shorter progression-free survival (p < 0.001) and overall survival (p < 0.001). Patients with high CHI3L1 expression also had a high risk of recurrence (p < 0.001) and death (p < 0.001). In vitro studies showed that CHI3L1 up-regulated the expression of anti-apoptotic Mcl-1 protein and hampered paclitaxel-induced apoptosis of ovarian cancer cells. These results suggest that CHI3L1 shows potential as a prognostic biomarker for EOC. CHI3L1 may promote chemoresistance via inhibition of drug-induced apoptosis by up-regulating Mcl-1.

Aside from tumor cells, ovarian cancer-related ascites contains the immune components. The aim of this study was to evaluate whether a combination of clinical and immunological parameters can predict survival in patients with ovarian cancer. Ascites specimens and medical records from 144 ovarian cancer patients at our hospital were used as the derivation group to select target clinical and immunological factors to generate a risk-scoring system to predict patient survival. Eighty-two cases from another hospital were used as the validation group to evaluate this system. The surgical status and expression levels of interleukin 17a (IL17a) and IL21 in ascites were selected for the risk-scoring system in the derivation group. The areas under the receiver operating characteristic (AUROC) curves of the overall score for disease-free survival (DFS) of the ovarian cancer patients were 0.84 in the derivation group, 0.85 in the validation group, and 0.84 for all the patients. The AUROC curves of the overall score for overall survival (OS) of cases were 0.78 in the derivation group, 0.76 in the validation group, and 0.76 for all the studied patients. Good correlations between overall risk score and survival of the ovarian cancer patients were demonstrated by sub-grouping all participants into four groups (P for trend

Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (P0.001), preserved ARID1A immunoreactivity (P=0.017) and infrequent PIK3CA mutation (P=0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age45 (P=0.045) and preserved ARID1A expression (P=0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P=0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P=0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy.

The overall survival (OS) of patients with ovarian cancer is poor while epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The aim of the present study was to evaluate the clinico-pathologic characteristics, especially the prognostic factors, for patients with epithelial ovarian cancer (EOC) in Taiwan. Information about newly diagnosed patients with EOC from 2009 to 2012 was retrieved from the database of the Taiwan Cancer Registry. Data from 2009 to 2013 for the respective cases from the claims database of Taiwan's National Health Insurance and National Death Registry were then retrieved. Potential prognostic factors were analyzed. The mean age at diagnosis of the 2,498 patients was 52.8 years. Serous carcinoma and clear cell carcinoma were diagnosed in 43.3% and 22.8% of the total patients, respectively. For patients with early-stage disease, taxane-based adjuvant chemotherapy, stage I, and younger age at diagnosis led to better overall survival (p = 0.030, p = 0.002, p

Objective Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. Methods Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. Results A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). Conclusion Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age.

Objective To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. Methods Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). Results There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07-0.68; p=0.010). Women in their 40s-50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03-1.49; p=0.020). Conclusion In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.

We analyzed the management and risk of subsequent cervical intraepithelial neoplasm 3 (CIN3) and invasive cervical cancer in women with low-grade squamous intraepithelial lesion (LSIL) cytology. A total of 53,293 women with a new diagnosis of cytologic LSIL were identified in Taiwan’s national cervical screening registration database. Based on the retrieved clinical management data, the incidence of subsequent CIN3+ lesions was determined, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. The average follow-up was 5.02 years. A total of 988 women developed CIN3+ lesions during this period, with an overall incidence of 369.3 women per 100,000 person-years. Cryotherapy and conization/loop electrosurgical excision procedure (LEEP) decreased the subsequent risk of CIN3+ lesions in women younger than 50 years (HR 0.49, 95% confidence interval [CI] 0.37–0.64, p

We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test), serous and mixed histological types (P = 0.003, Kruskal-Wallis test), malignant ascites (P = 0.009, chi-square test), and history of other drug allergy (P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

Objective To report a case of isolated omental peritoneal carcinoma without peritoneal carcinomatosis. Case report A 60-year-old female with abdominal distention was found to have a pelvic mass. Under the impression of ovarian cancer, laparotomy was performed only to show one isolated mass over omentum. Serial examination and pathology study including immunochemical staining indicated primary peritoneal serous carcinoma. Conclusion Isolated omental peritoneal carcinoma without peritoneal carcinomatosis and ascites is rare, and whether this represented a unique entity with different chemotherapy response and treatment outcome from the disseminated form of primary peritoneal carcinoma needs to be reviewed in the future.

Objective To investigate the clinical and pathological characteristics and the management of uterine papillary serous carcinoma (UPSC) in relation to patients' outcomes. Methods Clinicopathological data and the management of patients treated between 1991 and 2010 at 11 member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. The Kaplan–Meier method was used to generate survival curves, and factors predictive of outcome were compared using the log-rank test and Cox regression analysis. Results A total of 119 pure UPSC patients were recruited. Stages I, II, III, and IV were identified in 34.5%, 2.5%, 36.1%, and 26.9% of the patients, respectively. The recurrence rate was 20.5% in FIGO stage I/II disease and 55.2% in FIGO stage III/IV disease. The 5-year overall survival rates for the patients with stage I, II, III, and IV disease were 92.0%, 66.7%, 34.2%, and 17.3%, respectively. Multivariate analysis showed that tumor stage (stage III/IV hazard ratio [HR] 8.65, 95% confidence interval [CI] 3.00–24.9) and optimal cytoreduction (HR 0.40, 95% CI 0.22–0.73) independently influenced the overall survival rate of UPSC patients. In addition, optimal cytoreduction (HR 0.36, 95% CI 0.17–0.78) and the combination of chemotherapy and radiation (HR 0.11, 95% CI 0.04–0.37) improved the overall survival of the advanced stage (FIGO stage III/IV) UPSC patients. Conclusions UPSC represents an aggressive subtype of endometrial cancer commonly accompanied by extra-uterine disease. Comprehensive surgical staging with cytoreductive surgery is mandatory and beneficial for UPSC patients. Systemic chemotherapy combined with radiation should be considered as an adjuvant therapy for advanced stage UPSC patients.

BACKGROUND Whether patients with functional dyspepsia (FD) should receive Helicobacter pylori eradication therapy remains controversial. AIMS This meta-analysis was to evaluate the long-term effects of H. pylori eradication on dyspeptic symptoms of patients with FD, by selecting the most recent well-designed randomized controlled trials. METHODS English-language articles in the medical literature containing information on the long-term (≥ 12 mo) effects of H. pylori eradication on dyspeptic symptoms in patients with FD were identified by searching the Medline, PubMed, and EMBASE databases. The MeSH and/or keywords included Helicobacter pylori OR H. pylori OR HP; functional dyspepsia OR non-ulcer dyspepsia; eradication OR cure or treatment; and improvement OR resolution. The Review Manager 4.2.2 was used for the meta-analysis. RESULTS Fourteen randomized controlled studies were included in the meta-analysis. Improvements of dyspepsia symptoms in patients of eradication group were significantly better than in patients of the control group [odds ratio (OR), 1.38; 95% confidence interval (CI), 1.18-1.62] (Z=4.00, P

The ovarian cancer-associated ascites is an ideal material for evaluating the interaction between the host immune system and cancer cells in the tumor micro-environment. The aim of this study was to investigate whether the selected target cytokine expression levels in ascites could serve as an immune biomarker for predicting outcomes in ovarian cancer.Eighty-eight specimens of ovarian cancer-associated ascites were evaluated to select the target cytokine by a cytokine profiling kit. The 144 total samples were subsequently analyzed for this target cytokine. The correlation between the target cytokine and clinical characteristics was analyzed.Interferon-gamma (IFN-γ) was identified as the target cytokine. Higher levels of IFN-γ in the ascites of the tumor micro-environment were associated with advanced disease (p=0.012), higher tumor histological grading (p=0.004), and sub-optimal surgical status (p=0.040). By multivariate analysis, the adjusted hazard ratios (HRs) were 2.74 (95% confidence interval (CI) 1.85-4.05, p0.001) for disease-free survival (DFS) and 1.72 (95% CI 1.01-2.93, p=0.048) for overall survival (OS) for a 10-fold increase in IFN-γ concentration in the ascites. An inverse dose-response relationship between IFN-γ level and survival was also noted (Ptrend0.001 for DFS and Ptrend0.042 for OS).Patients with ovarian cancer and higher IFN-γ expression levels in cancer-associated ascites will have shorter DFS and OS. IFN-γ levels in the ascites may be a prognostic marker and a potential reference for immunotherapy targeting IFN-γ.

Objective: To investigate the changes of incidence and prognosis of epithelial ovarian cancer in thirty years in Taiwan. Methods: The databases of women with epithelial ovarian cancer during the period from 1979 to 2008 were retrieved from the National Cancer Registration System of Taiwan. The incidence and prognosis of these patients were analyzed. Results: Totally 9,491 patients were included in the study. The age-adjusted incidences of epithelial ovarian cancer were 1.01, 1.37, 2.37, 3.24, 4.18, and 6.33 per 100,000 person-years, respectively, in every 5-year period from 1979 to 2008. The age-specific incidence rates increased especially in serous, endometrioid and clear cell carcinoma, and the age of diagnosis decreased from sixty to fifty years old in the three decades. Patients with mucinous, endometrioid, or clear cell carcinoma had better long-term survival than patients with serous carcinoma (log rank test, p

BACKGROUND The efficacy of afatinib, an irreversible ErbB Family Blocker, was evaluated in patients who had 1 of 4 categories of solid tumors with epidermal growth factor receptor/human epidermal growth factor receptor 2 (EGFR/HER2) gene amplification or EGFR-activating mutations. METHODS Patients with previously treated but ErbB inhibitor-naive esophagogastric, biliary tract, urothelial tract, or gynecologic cancers (lung cancers were excluded) harboring EGFR/HER2 gene amplification or high polysomy were identified by fluorescence in situ hybridization (FISH). Tumors were also screened for EGFR mutations. The primary endpoint was the objective response rate; secondary endpoints included the clinical benefit rate, pharmacokinetics, and safety. RESULTS Of 385 prescreened patients, 38 had FISH-positive tumors (10 with EGFR amplification and 29 with HER2 amplification or high polysomy [1 tumor had EGFR/HER2 high polysomy]; none had EGFR-activating mutations), and 20 patients received treatment with afatinib 50 mg daily. The objective response rate was 5% (1 of 20 patients), and the best objective response included 1 complete response. Eight patients experienced stable disease. The most frequently reported adverse events were diarrhea, rash, and decreased appetite. The trial closed early because of slow recruitment. CONCLUSIONS Single-agent afatinib activity was limited, yet encouraging, in selected tumors that were screened prospectively for target activation. The implementation of a biomarker-driven approach using a low-frequency biomarker for patient selection across multiple tumor types can be challenging. Cancer 2013;119:3043—3051. © 2013 American Cancer Society.

To investigate the role of lymphadenectomy in uterine endometrioid carcinoma based on the 2009 FIGO staging system.Using an institution-maintained cancer registry database, all patients who were treated surgically for endometrial cancer from 1991 to 2008 in two medical centers were analyzed. Kaplan-Meier and Cox proportional hazards methods were used to determine the role of lymphadenectomy.From 961 women with uterine endometrioid carcinoma, 680 underwent lymphadenectomy and 281 did not. Young age, early-stage disease, low-grade tumor, and lymphadenectomy were favorable independent prognostic factors. The five-year disease-specific survival (DSS) of stages IA, IB, II, and III, and the two-year DSS of stage IV patients who underwent lymphadenectomy were 97.8%, 88.3%, 91.5%, 70.5%, and 32.1%, respectively, compared to 98.7%, 70.0%, 73.3%, 42.9%, and 16.6% in those without lymphadenectomy (p0.05 for stage IA; p0.01 for stages IB-IV, log-rank test). In high-risk patients (i.e., poorly-differentiated, outer-half myometrial invasion, and stages II-IV), more extensive lymph node resection was associated with an improved five-year DSS, from 71.3% (1-10 nodes removed) and 85.3% (11-20 nodes removed) to 86.8% (20 nodes removed) (p = 0.02, log-rank test). For stage IIIC-IV patients with nodal metastasis, the extent of node resection also significantly improved the five-year DSS, from 34.4% (1-10 nodes removed) and 62.4% (11-20 nodes removed) to 79.6% (20 nodes removed) (p = 0.04, log-rank test).Lymphadenectomy improves the survival of patients with uterine endometrioid carcinoma stage IB to stage IV. The extent of lymphadenectomy also improves the survival of high-risk patients and those with nodal disease.

// Tsung-Ming Tsao 1 , Ming-Jer Tsai 1, 2 , Jing-Shiang Hwang 3 , Wen-Fang Cheng 4 , Chang-Fu Wu 5 , Charles-C.K. Chou 6 and Ta-Chen Su 5, 7 1 The Experimental Forest, National Taiwan University, Nantou, Taiwan 2 School of Forestry and Resource Conservation, National Taiwan University, Taipei, Taiwan 3 Institute of Statistical Science, Academia Sinica, Taipei, Taiwan 4 Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan 5 Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan 6 Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan 7 Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital, Taipei, Taiwan Correspondence to: Ta-Chen Su, email: tachensu@gmail.com Keywords: natural killer cells; activating NK cells; forest trip; forest environment; urban environment Received: January 05, 2017 Accepted: March 01, 2018 Published: March 27, 2018 ABSTRACT Health effect assessments based on natural killer (NK) cells are an important emerging area of human health. We recruited 90 forest staff members in Xitou, Taiwan and 110 urban staff members in Taipei to investigate the health effects of forest environment exposure on NK cells (CD3 − /CD56 + ) and activating NK cells (CD3 − /CD56 + /CD69 + ) in humans. We also invited 11 middle-aged volunteers in a pilot study to participate in a five-day/four-night forest trip to Xitou forest to investigate the health effects of a forest trip on NK cells and activating NK cells. Results showed that NK cells were higher in the forest group (19.5 ± 9.1%) than in the urban group (16.4 ± 8.4%). In particular, the percentage of NK cells was significantly higher in the forest group than in the urban group among the subgroups of male, a higher body mass index (≥ 25 kg/m 2 ), without hypertension, lower high-sensitivity C-reactive protein, hyperglycemia, without smoking habit, and with tea drinking habit. After the five-day trip in Xitou forest, the percentage of activating NK cells of the invited participants from Taipei increased significantly after the trip to Xitou forest (0.83 ± 0.39% vs. 1.72 ± 0.1%). The percentage of activating NK cells was 1.13 ± 0.43%, which was higher than the baseline value of 0.77 ± 0.38% before the forest trip among the seven subjects who participated in the follow-up study four days after returning to Taipei. This study suggests that exposure to forest environments might enhance the immune response of NK cells and activating NK cells in humans.

Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01–2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07–3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03–5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45–10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.

Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.

► Malignant struma ovarii can result in cerebral ischemic stroke and Trousseau's syndrome. ► The combination of anti-neoplastic and anti-coagulant therapy should be undertaken to treat and correct the malignancy-associated coagulopathy.

The alpha‐folate receptor (α‐FR) is highly‐expressed in various non‐mucinous tumors of epithelial origin, including ovarian carcinoma. The aim of this study was to investigate the relationship between alpha‐folate receptor (α‐FR) and the clinico‐pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of α‐FR to chemo‐resistance. Therefore, semi‐quantitative reverse‐transcription polymerase chain reactions for α‐FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of α‐FR in each ovarian cancer tissue specimen was defined as the ratio of density of α‐FR to density of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). In vitro apoptotic experiments were tested in the original OVCAR‐3 tumor cells and various OVCAR‐3 α‐FR‐transfectants. Patients with an increased α‐FR expression level had poorer responses to chemotherapy (per α‐FR expression level increase: odds ratio (OR): 8.97 (95% confidence interval (CI): 1.40–57.36), p = 0.021). An increased α‐FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per α‐FR expression level increase: hazard ratio (HR): 2.45 (95% CI: 1.16–5.18), p = 0.02) and had a negative impact on overall survival (OS) of these serous ovarian cancer patients (per α‐FR expression level increase: HR: 3.6 (95% CI: 0.93–13.29), p = 0.03) by multivariate analyses. α‐FR inhibited cytotoxic drug‐induced apoptosis in our in vitro apoptotic assays. α‐FR could induce chemo‐resistance via regulating the expression of apoptosis‐related molecules, Bcl‐2 and Bax. Therefore, α‐FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of ovarian cancer treatment.

Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts.Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (27 repeats) or L (≥ 27 repeats) alleles. Multivariate analyses were used to estimate the effect size after accounting for CV covariates.Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles.HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors.

The incidence of breast and genital tract cancers is increasing among Taiwanese women, but the age specificity and histopathological features of these cancers have not been determined. We used a descriptive epidemiological method and data from the Taiwan Cancer Registry (1979-2007) to examine secular trends in the age-specific incidences of female breast cancer, three major female genital tract cancers and the histopathological subtypes of these cancers. Age-specific incidence rates in the United States (1978-2002) were used as an external reference, and the incidence rates of all malignancies and of malignant brain tumors were used as internal references. We found that age-adjusted incidence rates of female breast, uterine, and ovarian cancers increased in Taiwan from 1979 to 2007, whereas the incidence of cervical cancer decreased after 1998. The largest increase was observed for ductal and lobular carcinomas of the breast and endometrioid carcinomas of the uterus and ovary in women ≤55 years, all of these tumors show a high prevalence of hormone receptor expressions. In addition, hormone-receptor-positive rates of breast cancer were uniquely higher in younger, as opposed to older, Taiwanese women. These findings indicate that estrogen-related cancers rapidly emerge in young women in Taiwan and that incidence rates are catching up with that of women living in the United States.

Objective To determine the incidence of cervical cancer and the age-specific survival from small cell cervical carcinoma in Taiwan. Design Retrospective study. Setting. Taiwan. Population Women diagnosed with cervical cancer from 1991 to 2005. Methods Analysis of data from the National Cancer Registration System and National Death Certification System. Main outcome measures Incidence and age at diagnosis of cervical carcinoma and age-specific and overall survival from small cell cervical carcinoma. Results During the study period, 36 122 women were diagnosed with cervical cancer, and 81.8% had squamous cell carcinoma (SCC). For the periods 1991-1995, 1996-2000 and 2001-2005, the mean age at diagnosis increased from 53.9 ± 13.3 to 55.0 ± 14.9 and then to 56.7 ± 14.7 years, respectively. The incidence of SCC decreased from 1991 to 2005. During the same period, non-significant increases of adenocarcinoma and small cell carcinoma were noted. For SCC, occurrence peaked in 1991-1995 in patients 50-59 years of age. From 1996 to 2005, it peaked in patients 40-49 years of age. For cervical adenocarcinoma, occurrence peaked in patients 40-49 years of age, with a steady increase in this age group from 1991 to 2005. Occurrence of small cell cervical carcinoma peaked in the period 1991-1995 in patients 30-39 years of age. During the 15 years of the study, the overall mortality rate of the 198 patients with small cell cervical carcinoma was 65.7%. Conclusions In Taiwan, the incidence of small cell cervical carcinoma and adenocarcinoma tended to increase, but the incidence of squamous cell cervical carcinoma significantly decreased during the period 1991-2005.

The present study aimed to evaluate a novel fluorescence in situ hybridization (FISH) assay for detecting the high-risk human papillomavirus (HR-HPV) DNA and signal pattern in cervical cytology specimens and for identifying cervical intraepithelial neoplasia (CIN) lesions. One hundred and ninety-six liquid-based cytology specimens with CIN were recruited. The signal pattern (punctate, mixed punctate and diffuse, and diffuse) detected by FISH was compared with E6 mRNA and correlated with histological classification. FISH and E6-type specific polymerase chain reaction (PCR) had fair to good agreement for detecting HPV DNA across all grades of CIN (kappa coefficient, 0.37–0.73). Among 44 samples of negative FISH and positive E6 type-specific PCR in HPV 16, 18, 31, 33, 52 and 58, 82% (36/44) of E6 mRNA were not detected, in contrast to 41% (48/118) of positive FISH and positive E6 type-specific PCR (p

This paper aims to evaluate the clinical characteristics of ovarian cancer patients with cerebral metastases. Ten ovarian cancer patients with brain metastases were retrospectively identified from a total of 539 ovarian cancer patients. Their characteristics before and at the time of diagnosis of cerebral metastases were analysed. The survival of them was also measured. Ten (1.9%) of the 539 ovarian cancer patients had brain metastases in the study period. Nine had stage III or IV tumours with either moderate or poor histological differentiation. The mean time from diagnosis of ovarian cancer to documentation of central nervous system metastasis was 24.3 months, which was 11.1 months if other sites of metastasis were involved before cerebral relapse. All of the patients with intra-cranial tumours suffered from associated neurological defects and relived by treatments. The median survival time after diagnosis of central nervous system involvement was 3 months. In this study, all ovarian cancer patients with cerebral metastases had clinical neurological symptoms. Physicians should pay more attention to ovarian cancer patients with neurological defects and arrange brain imaging studies for the early diagnosis of brain metastases and prompt management to improve quality of life.